FER_MOUSE
ID FER_MOUSE Reviewed; 823 AA.
AC P70451; Q61561; Q6PEE5; Q80UI3; Q8C481; Q9EQ77;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Tyrosine-protein kinase Fer;
DE EC=2.7.10.2;
DE AltName: Full=Proto-oncogene c-Fer;
DE AltName: Full=p94-Fer;
GN Name=Fer; Synonyms=Fert2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Letwin K., Pawson T.;
RT "Murine Fer.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AUTOPHOSPHORYLATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=2294399; DOI=10.1128/mcb.10.1.146-153.1990;
RA Fischman K., Edman J.C., Shackleford G.M., Turner J.A., Rutter W.J.,
RA Nir U.;
RT "A murine fer testis-specific transcript (ferT) encodes a truncated Fer
RT protein.";
RL Mol. Cell. Biol. 10:146-153(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, AUTOPHOSPHORYLATION,
RP INTERACTION WITH IRS1 AND PIK3R1, AND SUBUNIT.
RX PubMed=11006284; DOI=10.1074/jbc.m006665200;
RA Iwanishi M., Czech M.P., Cherniack A.D.;
RT "The protein-tyrosine kinase fer associates with signaling complexes
RT containing insulin receptor substrate-1 and phosphatidylinositol 3-
RT kinase.";
RL J. Biol. Chem. 275:38995-39000(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J, and FVB/N-3; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 125-823 (ISOFORM 5).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, AND INTERACTION
RP WITH CTNND1 AND PDGFR.
RX PubMed=7623846; DOI=10.1128/mcb.15.8.4553;
RA Kim L., Wong T.W.;
RT "The cytoplasmic tyrosine kinase FER is associated with the catenin-like
RT substrate pp120 and is activated by growth factors.";
RL Mol. Cell. Biol. 15:4553-4561(1995).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF TMF1, AUTOPHOSPHORYLATION, MUTAGENESIS OF
RP GLY-571, AND CHARACTERIZATION OF ISOFORM 4.
RX PubMed=9742951; DOI=10.1016/s0014-5793(98)01003-5;
RA Schwartz Y., Ben-Dor I., Navon A., Motro B., Nir U.;
RT "Tyrosine phosphorylation of the TATA element modulatory factor by the FER
RT nuclear tyrosine kinases.";
RL FEBS Lett. 434:339-345(1998).
RN [8]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-715, AND MUTAGENESIS OF
RP TYR-715.
RX PubMed=10074905;
RA Ben-Dor I., Bern O., Tennenbaum T., Nir U.;
RT "Cell cycle-dependent nuclear accumulation of the p94fer tyrosine kinase is
RT regulated by its NH2 terminus and is affected by kinase domain integrity
RT and ATP binding.";
RL Cell Growth Differ. 10:113-129(1999).
RN [9]
RP CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, MUTAGENESIS OF 135-LYS-LEU-136;
RP 322-MET-LEU-323; LYS-592 AND ASP-743, AUTOPHOSPHORYLATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10391941; DOI=10.1074/jbc.274.28.19934;
RA Craig A.W., Zirngibl R., Greer P.;
RT "Disruption of coiled-coil domains in Fer protein-tyrosine kinase abolishes
RT trimerization but not kinase activation.";
RL J. Biol. Chem. 274:19934-19942(1999).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3,
RP AUTOPHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=10878010; DOI=10.1074/jbc.m003402200;
RA Priel-Halachmi S., Ben-Dor I., Shpungin S., Tennenbaum T., Molavani H.,
RA Bachrach M., Salzberg S., Nir U.;
RT "FER kinase activation of Stat3 is determined by the N-terminal sequence.";
RL J. Biol. Chem. 275:28902-28910(2000).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=11339827; DOI=10.1006/excr.2001.5217;
RA Zirngibl R., Schulze D., Mirski S.E., Cole S.P., Greer P.A.;
RT "Subcellular localization analysis of the closely related Fps/Fes and Fer
RT protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular
RT trafficking.";
RL Exp. Cell Res. 266:87-94(2001).
RN [12]
RP DISRUPTION PHENOTYPE, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=11134346; DOI=10.1128/mcb.21.2.603-613.2001;
RA Craig A.W., Zirngibl R., Williams K., Cole L.A., Greer P.A.;
RT "Mice devoid of fer protein-tyrosine kinase activity are viable and fertile
RT but display reduced cortactin phosphorylation.";
RL Mol. Cell. Biol. 21:603-613(2001).
RN [13]
RP INTERACTION WITH PLEC.
RX PubMed=12200133; DOI=10.1016/s0006-291x(02)02007-7;
RA Lunter P.C., Wiche G.;
RT "Direct binding of plectin to Fer kinase and negative regulation of its
RT catalytic activity.";
RL Biochem. Biophys. Res. Commun. 296:904-910(2002).
RN [14]
RP FUNCTION IN RESPONSE TO LIPOPOLYSACCHARIDE AND LEUKOCYTE DIAPEDESIS.
RX PubMed=11994443; DOI=10.4049/jimmunol.168.10.4930;
RA McCafferty D.M., Craig A.W., Senis Y.A., Greer P.A.;
RT "Absence of Fer protein-tyrosine kinase exacerbates leukocyte recruitment
RT in response to endotoxin.";
RL J. Immunol. 168:4930-4935(2002).
RN [15]
RP DISRUPTION PHENOTYPE.
RX PubMed=12901971; DOI=10.1016/s0301-472x(03)00107-3;
RA Senis Y.A., Craig A.W., Greer P.A.;
RT "Fps/Fes and Fer protein-tyrosine kinases play redundant roles in
RT regulating hematopoiesis.";
RL Exp. Hematol. 31:673-681(2003).
RN [16]
RP INDUCTION BY INSULIN, AND INTERACTION WITH STAT3 AND JAK1.
RX PubMed=12738762; DOI=10.1210/me.2002-0328;
RA Taler M., Shpungin S., Salem Y., Malovani H., Pasder O., Nir U.;
RT "Fer is a downstream effector of insulin and mediates the activation of
RT signal transducer and activator of transcription 3 in myogenic cells.";
RL Mol. Endocrinol. 17:1580-1592(2003).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF PTPN1.
RX PubMed=15226396; DOI=10.1242/jcs.01174;
RA Xu G., Craig A.W., Greer P., Miller M., Anastasiadis P.Z., Lilien J.,
RA Balsamo J.;
RT "Continuous association of cadherin with beta-catenin requires the non-
RT receptor tyrosine-kinase Fer.";
RL J. Cell Sci. 117:3207-3219(2004).
RN [18]
RP INTERACTION WITH TMF1.
RX PubMed=15467733; DOI=10.1038/sj.onc.1208149;
RA Perry E., Tsruya R., Levitsky P., Pomp O., Taller M., Weisberg S.,
RA Parris W., Kulkarni S., Malovani H., Pawson T., Shpungin S., Nir U.;
RT "TMF/ARA160 is a BC-box-containing protein that mediates the degradation of
RT Stat3.";
RL Oncogene 23:8908-8919(2004).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF CTTN, PHOSPHORYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16176974; DOI=10.1091/mbc.e05-05-0410;
RA El Sayegh T.Y., Arora P.D., Fan L., Laschinger C.A., Greer P.A.,
RA McCulloch C.A., Kapus A.;
RT "Phosphorylation of N-cadherin-associated cortactin by Fer kinase regulates
RT N-cadherin mobility and intercellular adhesion strength.";
RL Mol. Biol. Cell 16:5514-5527(2005).
RN [20]
RP FUNCTION IN MAST CELL ACTIVATION, FUNCTION IN PHOSPHORYLATION OF PECAM1,
RP PHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=16731527; DOI=10.1074/jbc.m604252200;
RA Udell C.M., Samayawardhena L.A., Kawakami Y., Kawakami T., Craig A.W.;
RT "Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to
RT platelet-endothelial cell adhesion molecule 1 to limit mast cell
RT activation.";
RL J. Biol. Chem. 281:20949-20957(2006).
RN [21]
RP FUNCTION, MUTAGENESIS OF PHE-606, AND INTERACTION WITH PPP1CA.
RX PubMed=16732323; DOI=10.1038/sj.onc.1209695;
RA Pasder O., Shpungin S., Salem Y., Makovsky A., Vilchick S., Michaeli S.,
RA Malovani H., Nir U.;
RT "Downregulation of Fer induces PP1 activation and cell-cycle arrest in
RT malignant cells.";
RL Oncogene 25:4194-4206(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [23]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=17606629; DOI=10.1128/mcb.01744-06;
RA Sangrar W., Gao Y., Scott M., Truesdell P., Greer P.A.;
RT "Fer-mediated cortactin phosphorylation is associated with efficient
RT fibroblast migration and is dependent on reactive oxygen species generation
RT during integrin-mediated cell adhesion.";
RL Mol. Cell. Biol. 27:6140-6152(2007).
RN [24]
RP FUNCTION IN STAT3 PHOSPHORYLATION, INTERACTION WITH HSP90, PHOSPHORYLATION
RP AT TYR-616, MUTAGENESIS OF TYR-616, UBIQUITINATION, AND PROTEASOMAL
RP DEGRADATION.
RX PubMed=19159681; DOI=10.1016/j.cellsig.2008.12.011;
RA Hikri E., Shpungin S., Nir U.;
RT "Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required
RT for the Fer tyrosine kinase activity.";
RL Cell. Signal. 21:588-596(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [27]
RP FUNCTION IN NEURONAL CELL DEATH AFTER BRAIN DAMAGE, AND INTERACTION WITH
RP NRP1.
RX PubMed=20133938; DOI=10.1074/jbc.m109.080689;
RA Jiang S.X., Whitehead S., Aylsworth A., Slinn J., Zurakowski B., Chan K.,
RA Li J., Hou S.T.;
RT "Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-
RT induced death of cortical neurons.";
RL J. Biol. Chem. 285:9908-9918(2010).
CC -!- FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface
CC receptors for growth factors and plays a role in the regulation of the
CC actin cytoskeleton, microtubule assembly, lamellipodia formation, cell
CC adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT,
CC PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-
CC kappa-B and cell proliferation. May play a role in the regulation of
CC the mitotic cell cycle. Plays a role in the insulin receptor signaling
CC pathway and in activation of phosphatidylinositol 3-kinase. Acts
CC downstream of the activated FCER1 receptor and plays a role in FCER1
CC (high affinity immunoglobulin epsilon receptor)-mediated signaling in
CC mast cells. Plays a role in the regulation of mast cell degranulation.
CC Plays a role in leukocyte recruitment and diapedesis in response to
CC bacterial lipopolysaccharide (LPS). Phosphorylates CTTN, CTNND1,
CC PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1.
CC Can phosphorylate STAT3 according to PubMed:10878010 and
CC PubMed:19159681, but clearly plays a redundant role in STAT3
CC phosphorylation. According to PubMed:11134346, cells where wild type
CC FER has been replaced by a kinase-dead mutant show no reduction in
CC STAT3 phosphorylation. Phosphorylates TMF1. Isoform 3 lacks kinase
CC activity. {ECO:0000269|PubMed:10878010, ECO:0000269|PubMed:11006284,
CC ECO:0000269|PubMed:11994443, ECO:0000269|PubMed:15226396,
CC ECO:0000269|PubMed:16176974, ECO:0000269|PubMed:16731527,
CC ECO:0000269|PubMed:16732323, ECO:0000269|PubMed:17606629,
CC ECO:0000269|PubMed:19159681, ECO:0000269|PubMed:20133938,
CC ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9742951}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:10391941};
CC -!- ACTIVITY REGULATION: Activated by phosphatidic acid binding (By
CC similarity). Activated by hydrogen peroxide (in vitro). Activated by
CC reactive oxygen species (ROS). {ECO:0000250,
CC ECO:0000269|PubMed:16731527, ECO:0000269|PubMed:17606629}.
CC -!- SUBUNIT: Homotrimer. Isoform 4 is a monomer, due to the absence of the
CC N-terminal coiled coil domains. Interacts with CTNND1, EGFR, FLT3,
CC PECAM1 and PDGFR. Interacts (via SH2 domain) with CTTN. Component of a
CC complex that contains at least FER, CTTN and PTK2/FAK1 (By similarity).
CC Interacts with IRS1 and PIK3R1. Interacts with STAT3. Interacts with
CC PPP1CA and regulates its phosphorylation at 'Thr-320'. Interacts with
CC JAK1. Interacts with HSP90; this stabilizes phosphorylated FER and
CC protects FER against proteasomal degradation. Interacts with ARHGDIA,
CC NRP1, PLEC and TMF1. {ECO:0000250, ECO:0000269|PubMed:10391941,
CC ECO:0000269|PubMed:10878010, ECO:0000269|PubMed:11006284,
CC ECO:0000269|PubMed:12200133, ECO:0000269|PubMed:12738762,
CC ECO:0000269|PubMed:15467733, ECO:0000269|PubMed:16732323,
CC ECO:0000269|PubMed:19159681, ECO:0000269|PubMed:20133938,
CC ECO:0000269|PubMed:7623846}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Cell projection {ECO:0000250}. Cell junction
CC {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Nucleus. Cytoplasm, cell
CC cortex {ECO:0000250}. Note=Detected on microtubules in polarized and
CC motile vascular endothelial cells. Colocalizes with F-actin at the cell
CC cortex. Colocalizes with PECAM1 and CTNND1 at nascent cell-cell
CC contacts (By similarity). Not detected in the nucleus, but detected in
CC the nuclear area surrounding the chromosomes after breakdown of the
CC nuclear envelope during mitosis (PubMed:11339827). {ECO:0000250,
CC ECO:0000269|PubMed:11339827}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P70451-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P70451-2; Sequence=VSP_021634;
CC Name=3; Synonyms=iFer;
CC IsoId=P70451-3; Sequence=VSP_041769, VSP_041770;
CC Name=4; Synonyms=FerT, p51FerT;
CC IsoId=P70451-4; Sequence=VSP_041766, VSP_041767, VSP_041768;
CC Name=5;
CC IsoId=P70451-5; Sequence=VSP_041768;
CC -!- TISSUE SPECIFICITY: Detected in liver and testis. Isoform 4 is detected
CC only in testis (at protein level). Widely expressed.
CC {ECO:0000269|PubMed:10391941, ECO:0000269|PubMed:11134346,
CC ECO:0000269|PubMed:2294399}.
CC -!- INDUCTION: Up-regulated by insulin in myogenic cells (in vitro).
CC {ECO:0000269|PubMed:12738762}.
CC -!- DOMAIN: The coiled coil domains mediate homooligomerization and are
CC required for location at microtubules. {ECO:0000250}.
CC -!- DOMAIN: The N-terminal region including the first coiled coil domain
CC mediates interaction with phosphoinositide-containing membranes.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:10074905,
CC ECO:0000269|PubMed:16176974, ECO:0000269|PubMed:16731527,
CC ECO:0000269|PubMed:19159681}.
CC -!- PTM: Polyubiquitinated; this leads to proteasomal degradation.
CC {ECO:0000269|PubMed:19159681}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype, and the mice are fertile.
CC Mice have reduced CTTN phosphorylation. Mice lacking both Fps/Fes and
CC Fer activity are viable and fertile, but produce slightly fewer pups
CC per litter than normal. They display elevated levels of circulating
CC neutrophils, erythrocytes and platelets, while other cell counts are
CC normal. {ECO:0000269|PubMed:11134346, ECO:0000269|PubMed:12901971}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fes/fps subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U76762; AAB18988.1; -; mRNA.
DR EMBL; M32054; AAA37617.1; -; mRNA.
DR EMBL; AF286537; AAG40730.1; -; mRNA.
DR EMBL; BC051249; AAH51249.1; -; mRNA.
DR EMBL; BC058100; AAH58100.1; -; mRNA.
DR EMBL; AK082799; BAC38626.1; -; mRNA.
DR CCDS; CCDS28936.1; -. [P70451-1]
DR CCDS; CCDS28937.1; -. [P70451-4]
DR CCDS; CCDS89132.1; -. [P70451-2]
DR PIR; I49663; I49663.
DR RefSeq; NP_001033086.2; NM_001037997.3. [P70451-1]
DR RefSeq; NP_001273344.1; NM_001286415.1. [P70451-2]
DR RefSeq; NP_032026.2; NM_008000.2. [P70451-4]
DR RefSeq; XP_006523703.1; XM_006523640.3. [P70451-1]
DR RefSeq; XP_006523704.1; XM_006523641.3. [P70451-1]
DR RefSeq; XP_006523706.1; XM_006523643.3. [P70451-5]
DR RefSeq; XP_011244595.1; XM_011246293.2. [P70451-5]
DR AlphaFoldDB; P70451; -.
DR SMR; P70451; -.
DR BioGRID; 199633; 4.
DR IntAct; P70451; 1.
DR MINT; P70451; -.
DR STRING; 10090.ENSMUSP00000000129; -.
DR iPTMnet; P70451; -.
DR PhosphoSitePlus; P70451; -.
DR jPOST; P70451; -.
DR MaxQB; P70451; -.
DR PaxDb; P70451; -.
DR PeptideAtlas; P70451; -.
DR PRIDE; P70451; -.
DR ProteomicsDB; 272987; -. [P70451-1]
DR ProteomicsDB; 272988; -. [P70451-2]
DR ProteomicsDB; 272989; -. [P70451-3]
DR ProteomicsDB; 272990; -. [P70451-4]
DR ProteomicsDB; 272991; -. [P70451-5]
DR Antibodypedia; 2083; 600 antibodies from 40 providers.
DR DNASU; 14158; -.
DR Ensembl; ENSMUST00000000129; ENSMUSP00000000129; ENSMUSG00000000127. [P70451-1]
DR Ensembl; ENSMUST00000038080; ENSMUSP00000037418; ENSMUSG00000000127. [P70451-4]
DR Ensembl; ENSMUST00000233190; ENSMUSP00000156523; ENSMUSG00000000127. [P70451-2]
DR GeneID; 14158; -.
DR KEGG; mmu:14158; -.
DR UCSC; uc008dfo.2; mouse. [P70451-2]
DR UCSC; uc008dfp.1; mouse. [P70451-3]
DR UCSC; uc008dfq.3; mouse. [P70451-1]
DR UCSC; uc008dfr.2; mouse. [P70451-5]
DR UCSC; uc008dfs.2; mouse. [P70451-4]
DR CTD; 2241; -.
DR MGI; MGI:105917; Fer.
DR VEuPathDB; HostDB:ENSMUSG00000000127; -.
DR eggNOG; KOG0194; Eukaryota.
DR GeneTree; ENSGT00940000154997; -.
DR HOGENOM; CLU_005265_0_0_1; -.
DR InParanoid; P70451; -.
DR OMA; NQFQQLT; -.
DR PhylomeDB; P70451; -.
DR TreeFam; TF315363; -.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR BioGRID-ORCS; 14158; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Fer; mouse.
DR PRO; PR:P70451; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P70451; protein.
DR Bgee; ENSMUSG00000000127; Expressed in spermatid and 240 other tissues.
DR ExpressionAtlas; P70451; baseline and differential.
DR Genevisible; P70451; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0045098; C:type III intermediate filament; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0070097; F:delta-catenin binding; ISO:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0045295; F:gamma-catenin binding; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IPI:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0034333; P:adherens junction assembly; IEA:Ensembl.
DR GO; GO:0120179; P:adherens junction disassembly; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IEA:InterPro.
DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; IMP:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; ISO:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IMP:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0050904; P:diapedesis; IMP:UniProtKB.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; IMP:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0038028; P:insulin receptor signaling pathway via phosphatidylinositol 3-kinase; IDA:UniProtKB.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISO:MGI.
DR GO; GO:0038109; P:Kit signaling pathway; IMP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0010762; P:regulation of fibroblast migration; IMP:UniProtKB.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IBA:GO_Central.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0036119; P:response to platelet-derived growth factor; IDA:UniProtKB.
DR GO; GO:0060009; P:Sertoli cell development; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; ISO:MGI.
DR CDD; cd07686; F-BAR_Fer; 1.
DR CDD; cd10361; SH2_Fps_family; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028539; Fer.
DR InterPro; IPR037452; Fer_F-BAR.
DR InterPro; IPR035849; Fes/Fps/Fer_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR016250; Tyr-prot_kinase_Fes/Fps.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR PANTHER; PTHR24418:SF227; PTHR24418:SF227; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR PIRSF; PIRSF000632; TyrPK_fps; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasm; Cytoskeleton; Kinase;
KW Lipid-binding; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; SH2 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..823
FT /note="Tyrosine-protein kinase Fer"
FT /id="PRO_0000260825"
FT DOMAIN 1..259
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 461..551
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 564..817
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..300
FT /note="Important for interaction with membranes containing
FT phosphoinositides"
FT /evidence="ECO:0000250"
FT REGION 389..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 123..185
FT /evidence="ECO:0000255"
FT COILED 301..381
FT /evidence="ECO:0000255"
FT ACT_SITE 685
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 570..578
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 592
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 402
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16591"
FT MOD_RES 616
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19159681"
FT MOD_RES 715
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10074905"
FT VAR_SEQ 1..369
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2294399"
FT /id="VSP_041766"
FT VAR_SEQ 70..127
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021634"
FT VAR_SEQ 370..412
FT /note="LRCTEAKCAAQKALLEQKVQENDGKEPPPVVNYEEDARSVTSM -> MDKSM
FT ECPHCEGVLEPESDPQFSKKCSIPLSPGPSSSEILRYK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:2294399"
FT /id="VSP_041767"
FT VAR_SEQ 444
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:2294399"
FT /id="VSP_041768"
FT VAR_SEQ 491..542
FT /note="GEYVLSVYSDGQRRHFIIQFVDNLYRFEGTGFSNIPQLIDHHFNTKQVITKK
FT -> ESVSIRGHRVFKHSPAYRSPLQYKASHHQEVWGGSAQPHPKG (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:11006284"
FT /id="VSP_041769"
FT VAR_SEQ 543..823
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11006284"
FT /id="VSP_041770"
FT MUTAGEN 135..136
FT /note="KL->RP: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:10391941"
FT MUTAGEN 322..323
FT /note="ML->RP: Abolishes homooligomerization."
FT /evidence="ECO:0000269|PubMed:10391941"
FT MUTAGEN 571
FT /note="G->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:9742951"
FT MUTAGEN 592
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10391941"
FT MUTAGEN 606
FT /note="F->A: Abolishes interaction with PPP1CA."
FT /evidence="ECO:0000269|PubMed:16732323"
FT MUTAGEN 616
FT /note="Y->F: Abolishes autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19159681"
FT MUTAGEN 715
FT /note="Y->F: Abolishes autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10074905"
FT MUTAGEN 743
FT /note="D->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10391941"
FT CONFLICT 328
FT /note="A -> G (in Ref. 5; BAC38626)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="T -> S (in Ref. 1; AAB18988 and 3; AAG40730)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="P -> A (in Ref. 2; AAA37617)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 823 AA; 94579 MW; F4C22E1E63721663 CRC64;
MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKESTVQ
VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ
IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM
LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDDYS QITSLVTEEI
VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL
TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES FETCEKKSDI VLLLGQKQAL
EELKQSVQQL RCTEAKCAAQ KALLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK
FESIRHSIAG IIKSPKSVLG SSTQVCDVIS VGERPLAEHD WYHGAIPRIE AQELLKQQGD
FLVRESHGKP GEYVLSVYSD GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT
KKSGVVLLNP IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA IKTCKEDLPQ
ELKIKFLQEA KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLTFL RKRKDELKLK
QLVRFSLDVA AGMLYLESKN CIHRDLAARN CLVGENNTLK ISDFGMSRQE DGGVYSSSGL
KQIPIKWTAP EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM
SAPQNCPEEV FTIMMKCWDY KPENRPKFND LHKELTVIKK MIT
